Levels of Evidence on Cholesterol’s Role in Atherosclerosis

There are several ways of demonstrating the major role not only of total cholesterol but mainly its low density lipoprotein fraction on the origin of the fatty streaks that can evolve into atherosclerotic plaques. Different approaches lead to the same assertion as can be verified by levels of research that approach the topic. The first studies were experimental. Conversion of fatty streaks into fibrous plaques: during long periods of feeding animals with cholesterol, there is finally deposition of connective tissue and development of a fibrous layer. The Framingham study was the one with the longest longitudinal follow-up time, establishing the concepts of cardiovascular epidemiology. Conceived in the city of Framingham, it followed a cohort of 6,000 individuals in order to investigate the risk factors correlated with the development of atherosclerotic disease. Over the course of 20 years, the study confirmed the importance of high levels of low-density lipoprotein cholesterol (LDL-C) and reduction of high-density lipoprotein cholesterol (HDL-C). Probably one of the first indications that coronary artery disease was related to cholesterol came from anecdotal case reports of children with xanthomas, who had sudden death or myocardial infarction before the age of 10. The first cases of homozygous familial hypercholesterolemia were described. Several researchers have described familial hypercholesterolemia as a genetic, monogenic alteration with a risk of early coronary artery disease, secondary to serum cholesterol elevations. The importance of LDL-C in atherogenesis can be explained in various contexts as represented by experimental researches, epidemiological data and genetic studies.